Bryostatin and Vincristine in B-Cell Malignancies

Recurrent Mantle Cell Lymphoma Clinical Trial

Official title:

A Phase I Trial of Combination Bryostatin 1 (NSC 339555) and Vincristine in B-Cell Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003166
• Other study ID #: NCI-2012-03120
• Secondary ID: CWRU 3Y97U01CA06
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: January 10, 2013
• Start date: May 1998

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This phase I trial is studying the side effects and best dose of bryostatin-1 when given together with vincristine in treating patients with chronic lymphocytic leukemia, non-Hodgkin's lymphoma, or multiple myeloma. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells

Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of bryostatin 1 as a 24 hour infusion and vincristine when administered sequentially.

II. To determine the effect of this combination on programmed cell death (apoptosis).

III. To determine the immunomodulatory effect of bryostatin 1. IV. To observe patients for clinical antitumor response after giving combination bryostatin 1 and vincristine.

OUTLINE: This is a dose-escalation study of bryostatin 1.

Patients receive bryostatin 1 IV over 24 hours followed immediately by vincristine IV. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients completing 6 courses of therapy may receive subsequent courses every 3 weeks and then every 4 weeks after 24 months of treatment. Patients may return to a 2- or 3-week treatment course at the discretion of the principal investigator.

Cohorts of 3 patients receive escalating doses of bryostatin 1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 1 of 3 patients experience dose-limiting toxicity.

Patients are followed every 3 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. primary completion date: July 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with biopsy proven B-cell malignancies [e.g. chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM)]; HIV-associated lymphomas and acute leukemias are not eligible

• Performance status: ECOG 0, 1, or 2

• Life expectancy of at least 12 weeks

• Patients with aggressive NHL will be enrolled after having failed all possible therapy with curative intent

• Patients with CLL must have failed an alkylating agent-containing regimen as well as fludarabine chemotherapy

• Patients with multiple myeloma must have received at least one prior chemotherapy regimen and not be eligible for a dose intensification treatment approach

• At least 4 weeks must have elapsed since prior large-field radiation therapy

• Patients must have been off previous anti-cancer therapy for at least 3 weeks (6 weeks for BCNU and mitomycin C) and recovered from all treatment related toxicity

• Prior vincristine therapy is allowed

• Sexually active men and women must use an accepted and effective method of contraception

• In women of child-bearing age, a pregnancy test may be done at the discretion of the investigator

• Must have given written informed consent

Exclusion Criteria:

• Patients with brain metastasis, leptomeningeal involvement, primary CNS NHL, and acute leukemia are ineligible

• Patients with HIV infection are ineligible

• WBC < 3000/ul

• Granulocytes < 1500/ul

• Platelets < 50,000/ul

• Hemoglobin =< 8.5 g/dl

• Bilirubin > 1.5 mg/dl

• AST and ALT > 2 times normal

• Creatinine > 2.0 mg/dl, and/or actual creatinine clearance < 40 ml/min/1.73 m^2; all patients are required to have a 24 hr creatinine clearance

• Clinical evidence of bleeding diathesis

• ECOG Performance status 3 or 4

• Patients who are pregnant or lactating; vincristine can cause fetal harm

• Patients with clinically apparent neuropathy are ineligible (>= grade 2 neuropathy)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Burkitt Lymphoma
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Immunoblastic
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Recurrent Adult Burkitt Lymphoma
• Recurrent Adult Diffuse Large Cell Lymphoma
• Recurrent Adult Diffuse Mixed Cell Lymphoma
• Recurrent Adult Immunoblastic Large Cell Lymphoma
• Recurrent Adult Lymphoblastic Lymphoma
• Recurrent Grade 3 Follicular Lymphoma
• Recurrent Mantle Cell Lymphoma
• Refractory Chronic Lymphocytic Leukemia
• Refractory Multiple Myeloma
• Stage III Multiple Myeloma

Intervention

Drug:
• bryostatin 1
Given IV
• vincristine sulfate
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Case Western Reserve University	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD		2 weeks	Yes
Primary	Response rates		Up to 11 years	No